Cells of the monocyte/macrophage (MO) lineage play a significant role in the functional integrity of the immune system by processing antigenic material in a form that triggers specific T lymphocyte proliferation, and by direct participation in effector responses including tumor immunity. Because of the limitations inherent in current technology for identifying and purifying MO, there are gaps in our understanding of MO differentiation as it occurs within the bone marrow and tissues giving rise to the observed heterogeneity in both morphology and function. The discovery that distinct stages of lymphoid differentiation can be identified by the expression of unique membrane antigens suggests the possibility that a similar approach might be useful in delineating the maturational stages within the MO lineage. With this rationale, the specific aims of this research application are to develop a panel of hybridoma-derived monoclonal antibodies which identify antigens common to the MO lineage, antigens which may be specific for distinct morphological segments within this lineage, and antigens that may identify functional subsets of cells within segments. These monospecific reagents will then be used to investigate the functional role of the MO populations they identify and the possible functional relevance of the antigens themselves. The antibodies will also provide a tool for identifying cells representing stages of MO differentiation within bone marrow, blood, and parenchymal tissues. Similarly, antibodies marking MO populations may clarify the confusion that exists regarding the origin of the abnormal cell in various diseases of the reticuloendothelial system, possibly offering an additional means of diagnosis or even a rationale for specific immunotherapy. In summary, antibodies recognizing antigens specific for the MO lineage may profoundly augment our understanding of MO differentiation and function in health and disease.